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Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke: Meta-Analysis of Population-Based Studies Involving 17 180 Individuals.

TitleCirculating Monocyte Chemoattractant Protein-1 and Risk of Stroke: Meta-Analysis of Population-Based Studies Involving 17 180 Individuals.
Publication TypeJournal Article
Year of Publication2019
AuthorsGeorgakis MK, Malik R, Björkbacka H, Pana TAlexandru, Demissie S, Ayers C, Elhadad MA, Fornage M, Beiser AS, Benjamin EJ, S Boekholdt M, Engström G, Herder C, Hoogeveen RC, Koenig W, Melander O, Orho-Melander M, Schiopu A, Söderholm M, Wareham N, Ballantyne CM, Peters A, Seshadri S, Myint PK, Nilsson J, de Lemos JA
Secondary AuthorsDichgans M
JournalCirc Res
Volume125
Issue8
Pagination773-782
Date Published2019 09 27
ISSN1524-4571
KeywordsAdult, Aged, Atherosclerosis, Biomarkers, Chemokine CCL2, Female, Humans, Male, Middle Aged, Stroke
Abstract

Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02-1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00-1.42]; third quartile: 1.35 [1.14-1.59]; fourth quartile: 1.38 [1.07-1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.

DOI10.1161/CIRCRESAHA.119.315380
Alternate JournalCirc Res
PubMed ID31476962
PubMed Central IDPMC6763364
Grant ListUH3 NS100605 / NS / NINDS NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
RF1 AG059421 / AG / NIA NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
R01 HL076784 / HL / NHLBI NIH HHS / United States
R01 AG049607 / AG / NIA NIH HHS / United States
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
HHSN268201700002C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
U01 AG052409 / AG / NIA NIH HHS / United States
R01 AG028321 / AG / NIA NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States
U01 AG058589 / AG / NIA NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
UH2 NS100605 / NS / NINDS NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
75N92019D00031 / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States